Embryonic aneuploidy - the true "last barrier in assisted reproductive technology"?

Human embryonic aneuploidy may represent one of the final frontiers in assisted reproductive technology, primarily secondary to oocyte aneuploidy. Mammalian oocytes possess unique characteristics predisposing them to much higher rates of aneuploidy than sperm or most somatic cells. Some of these characteristics are age-independent, whereas others result from reproductive aging and environmental toxicity. A detailed understanding of these properties may lead to novel diagnostic and therapeutic tools designed to detect and prevent oocyte and embryonic aneuploidy to overcome this ultimate barrier to success in assisted reproductive technology.

Monitoring of controlled ovarian stimulation in IVF.

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

LH supplementation in IVF: human nature, politics, and elephants in the room.

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1. The different endocrinology between the long agonist and the antagonist protocols. 2. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. 3. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. CONCLUSIONS: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation.

Looking with new eyes: advanced microscopy and artificial intelligence in reproductive medicine.

Microscopy has long played a pivotal role in the field of assisted reproductive technology (ART). The advent of artificial intelligence (AI) has opened the door for new approaches to sperm and oocyte assessment and selection, with the potential for improved ART outcomes.

The DIY IVF cycle-harnessing the power of deeptech to bring ART to the masses.

The emergence of telehealth including telemedicine, at-home testing, and mobile health applications has enabled patients to self-manage their reproductive care, especially during the COVID-19 pandemic. Reproduction is rapidly changing and embracing deeptech initiatives that can improve outcomes and facilitate personalized fertility solutions in the near future. This so-called DIY IVF informed by deeptech and moderated by femtech not only holds a tremendous amount of promise, but also challenges and possible pitfalls. This review discusses the current status of deeptech and femtech for IVF care in a post-Roe v. Wade environment.

The role of growth hormone in assisted reproduction.

In contemporary ART, the use of "add-ons" during ovarian stimulation has increased, especially in poor responders. Growth Hormone (GH) is an adjunctive therapy that has been studied extensively in the translational and clinical setting, with an ongoing scientific debate over its effectiveness and optimal use. In this review, we aim to provide an overview of the physiologic basis for the use of GH in ART, and to summarize the latest evidence regarding its clinical use, primarily as an adjunct to ovarian stimulation, but also in the IVF lab and with regards to its effects on the endometrium.

Use of pulsatile gonadotropin-releasing hormone (GnRH) in patients with functional hypothalamic amenorrhea (FHA) results in monofollicular ovulation and high cumulative live birth rates: a 25-year cohort.

PURPOSE: To analyze outcomes of pulsatile administration of gonadotropin-releasing hormone (GnRH) in infertile women diagnosed with functional hypothalamic amenorrhea (FHA). METHODS: A single-center retrospective cohort study was conducted from 1996 to 2020. Sixty-six patients with the diagnosis FHA that underwent therapy using the pulsatile GnRH pump for conception were included and analyzed. The primary outcome was the live birth rate (LBR). Secondary outcomes were the number of dominant follicles, ovulation rate, biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate, and multiple pregnancy rate. A matched control group was selected to compare the birth weight of newborn children. RESULTS: During the study period, 66 patients with FHA underwent 82 treatments (14 of 66 patients had more than one treatment) and a total of 212 cycles (ovulation induction attempts) using pulsatile GnRH. The LBR per treatment was 65.9%. The ovulation rate per cycle was 96%, and monofollicular ovulation was observed in 75% of cycles. The BPR per treatment was 80.5%, and the cumulative CPR per treatment was 74.4%. The miscarriage rate was 11.5%. One dizygotic twin pregnancy was observed (1.6%). Average newborn birth weight (NBW) from patients with FHA was comparable to the control group. CONCLUSION(S): In patients with FHA, excellent pregnancy rates were achieved using the subcutaneous GnRH pump. The high cumulative LBR with normal NBW as well as low rates of multiple gestation indicate that the pulsatile GnRH pump represents a safer and more physiologic alternative to ovulation induction with injectable gonadotropins. TRIAL REGISTRATION: Ethics Committee Northwest and Central Switzerland (Ethikkommission Nordwest- und Zentralschweiz - EKNZ) - Project-ID 2020-01612.

Protecting life in a time of war.

Despite centuries of lessons from history, war endures. Across Earth, during nearly every year from the beginning of the twentieth century to present day, over 30 wars have been fought resulting in 187 million casualties, excluding the most recent conflict, which is the impetus for this essay (Timeline of 20th and 21st century wars). We are, sadly, a war-mongering people. The word "war" word infiltrates our vernacular, e.g., the war on poverty, on drugs, on cancer, on COVID, and, apropos, on terror. How did rational approaches to disagreement and conflict evade the world's progress? Reproductive physicians and scientists are dedicated to safeguard lives and build families. Violence is antithetical to our mission as professionals, and moral integrity as humans. We are deeply concerned for, and stand in unity with, our Ukrainian colleagues-the embryologists, scientists, OBGYN and REI physicians, infertility patients, and all people under siege. Reproductive health services for Ukrainians (as with many other war-torn regions) have collapsed. Deeply disturbing reports have emerged that cite civilian hospitals (including maternity centers) being targeted. Liquid nitrogen supplies are scarce. Pregnant mothers and gestational carriers are at emergent risk of delivering in extremely harsh conditions, cold underground bunkers and refugee queues.

Molar pregnancy after in vitro fertilization with euploid single embryo transfer.

OBJECTIVE: To describe a case of molar pregnancy after in vitro fertilization (IVF) resulting from the transfer of a euploid embryo derived from a monopronuclear zygote. DESIGN: Case report and review of the literature. SETTING: Private practice IVF center. PATIENTS: A 42-year-old woman, gravida 3 para 0, with advanced maternal age and infertility who underwent IVF. INTERVENTIONS: Preimplantation genetic testing for aneuploidy using next-generation sequencing, single frozen euploid blastocyst transfer, and medical management of suspected missed abortion. MAIN OUTCOME MEASURES: Genetic examination of products of conception and correlation with embryonic preimplantation genetic testing for aneuploidy results. RESULTS: Transfer of the euploid embryo derived from an abnormally fertilized oocyte (monopronuclear zygote) resulted in a clinical pregnancy suspected to be a missed abortion. Products of conception collected after medical management of the suspected missed abortion were analyzed using next-generation sequencing with the report "46,XX complete molar pregnancy". CONCLUSIONS: To our knowledge, this is the first account of a complete molar pregnancy resulting from the transfer of a reported euploid embryo, highlighting the importance of understanding the limitations of genetic testing platforms in the setting of abnormally fertilized oocyte-derived embryos.

Artificial intelligence-the future is now.

The pros and cons of artificial intelligence in assisted reproductive technology are presented.

Triggering change in stimulation protocols: a matter of oocyte maturation and beyond.

Since the birth of Louise Brown, in vitro fertilization (IVF) stimulation protocols have evolved significantly. One particular area of focus has been the process of final oocyte maturation, during which the oocyte gains competence to support fertilization and early embryonic development up to implantation. The field of human assisted reproductive technology (ART) is witnessing increased utilization of GnRH agonists (GnRHa) as trigger agents, in addition to or instead of the traditionally used human chorionic gonadotropin (hCG). Future translational studies will reveal whether oocyte developmental competence, as reflected in live birth outcomes, are not only non-inferior, but also superior with the use of GnRHa as a trigger for both nuclear and cytoplasmic oocyte maturation.

Frozen-thawed embryo transfers: time to adopt a more "natural" approach?

The increasing use of frozen-thawed embryo transfer (FET) cycles has magnified the focus on endometrial preparation protocols in assisted reproduction. Emerging evidence suggests that natural cycle (NC) FETs are associated with improved outcomes, and that providers should consider increasing the utilization of NC FET at the expense of the currently favored artificial cycle (AC) FET as primary method for endometrial preparation.